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Journal of Virology, April 2000, p. 3082-3092, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Structure and Coding Content of CST (BART) Family RNAs of Epstein-Barr Virus

Paul R. Smith,1 Orlando de Jesus,1 David Turner,1,2 Martine Hollyoake,3 Claudio Elgueta Karstegl,3 Beverly E. Griffin,2,dagger Lorraine Karran,2,Dagger Yilong Wang,4 S. Diane Hayward,4 and Paul J. Farrell1,3,*

Virology and Cell Biology,1 Ludwig Institute for Cancer Research,3 and Infectious Diseases and Microbiology,2 Imperial College School of Medicine, London W2 1PG, United Kingdom, and Department of Pharmacology, Johns Hopkins School of Medicine, Baltimore, Maryland 212054

Received 27 September 1999/Accepted 3 January 2000

CST (BART BARF0) family viral RNAs are expressed in several types of Epstein-Barr virus (EBV) infection, including EBV-associated cancers. Many different spliced forms of these RNAs have been described; here we have clarified the structures of some of the more abundant splicing patterns. We report the first cDNAs representing a full-length CST mRNA from a clone library and further characterize the transcription start. The relative abundance of splicing patterns and genomic analysis of the open reading frames (ORFs) suggest that, in addition to the much studied BARF0 ORF, there may be important products made from some of the upstream ORFs in the CST RNAs. Potential biological functions are identified for two of these. The product of the RPMS1 ORF is shown to be a nuclear protein that can bind to the CBF1 component of Notch signal transduction. RPMS1 can inhibit the transcription activation induced through CBF1 by NotchIC or EBNA-2. The protein product of another CST ORF, A73, is shown to be a cytoplasmic protein which can interact with the cell RACK1 protein. Since RACK1 modulates signaling from protein kinase C and Src tyrosine kinases, the results suggest a possible role for CST products in growth control, perhaps consistent with the abundant transcription of CST RNAs in cancers such as nasopharyngeal carcinoma.

* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 207 724 5522, ext. 203. Fax: 44 207 724 8586. E-mail: p.farrell{at}ic.ac.uk.

dagger Present address: Viral Oncology Unit, Division of Medicine, Imperial College School of Medicine, London W2 1PG, United Kingdom.

Dagger Present address: Academic Department of Haematology and Cytogenetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.

Journal of Virology, April 2000, p. 3082-3092, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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